Authors Horwich A, Fossa SD, Huddart R, Dearnaley DP, et al
Review Date March 2014
Citation Br J Cancer 2014;110 (1):256-263
Stage I testicular seminoma is usually diagnosed at a young age and treatment is associated with low relapse and mortality rates. For many years the treatment for stage 1 seminoma was orchidectomy with adjuvant radiotherapy. With surveillance a viable alternative to adjuvant radiotherapy, the long-term risks of adjuvant radiotherapy are important to consider in addition to the risk of relapse with each management option.
To increase the accuracy of risk estimates for second malignancies and mortality associated with adjuvant radiotherapy after surgery for stage 1 seminoma, by assessing outcomes in a group of patients treated as young adults, without confounding by chemotherapy or significant levels of diagnostic radiation, and with access to details of initial diagnosis, staging and treatment from participating radiotherapy centres (n=11 UK, I Norway).
Patients were identified from medical records and treatments details obtained from 12 cancer centres. Second cancers and mortality data were ascertained from national registries. Data from 2543 patients with stage 1 seminoma treated with radiotherapy between 1960 and 1992 were included in the analysis (management policies during this period were stable) followed up to December 2007 (51,151 person-years). The at-risk period was defined to start at one year after the start of radiotherapy. To calculate standardised mortality ratios (SMR) or incidence ratios (SIR), expected numbers of deaths and second cancers were based on those of the general populations of England and Wales or Norway during the same time periods.
Median age at diagnosis was 37.2 years (interquartile range 31.3 to 44.7). Radiotherapy details showed 91% had radiation to abdominal and pelvic lymph nodes.
The authors identified second cancers (excluding non-melanoma skin cancers). The SIR was 1.61 (95% confidence interval (CI): 1.47-1.76, P<0.0001). If second testicular cancers (n=32) were excluded the SIR was 1.53 (95% CI: 1.39-1.68, P<0.0001). This elevated risk of second cancers was mainly due to an excess of cancers in organs in the radiation field – for pelvic-abdominal sites the SIR was 1.62 (95% CI: 1.43-1.83) mainly bladder, pancreatic, stomach cancers – with no significant elevated risk of cancers in organs elsewhere in the body. SIR decreased with age at diagnosis (P<0.0001) and increased with time after radiotherapy (p<0.00001) and there was some evidence of a dose effect.
There was no overall increase in mortality with a SMR of 1.06 (95% CI: 0.98-1.14), despite an increase in the cancer-specific mortality (excluding testicular cancer deaths) SMR of 1.46 (95% CI: 1.30-1.65, P<0.0001).
The prognosis of stage 1 seminoma is excellent and the long-term risk of iatrogenic disease such as a second cancer is an important consideration in the choice of treatment following orchidectomy.
Points to Note
- The study showed an increased risk of second cancers in the radiation field (even when excluding second testicular cancers) in long-term follow-up of a large cohort of stage 1 seminoma patients, confirming findings of other studies.
- Other studies have suggested no significant increase in risk of second cancers (excluding testicular cancer) in patients treated by surgery alone but patient cohorts are not large enough to make conclusions yet. Risk of relapse with surveillance is thought to be about 15-20% but most are treated successfully.
- Cancer mortality rate was significantly elevated but not overall mortality rate, apparently due to lower mortality from circulatory and other non-cancer causes; the reason for this is not known.
- There was some confounding of the association with length of follow-up as average radiation dose reduced over time. There is also some evidence that reducing dose can reduce risk of second cancers.
- Ascertainment bias could be an issue in the study as the men treated with radiation generally have many years medical follow-up.
- Cure rate in patients with stage 1 seminoma is high whether treated post-orchidectomy with surveillance, adjuvant radiotherapy or adjuvant carboplatin chemotherapy. In this scenario, long term risks associated with adjuvant therapy are an important consideration in treatment decisions.